Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study

Abstract

Background and Objective Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses. Methods A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1β (IL-1β) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1β at statistical significance at genome-wide level (P < 5 × 10−8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger. Results Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00–1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00–1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1β) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01–1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02–1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017). Conclusions The findings suggests that periodontitis and the higher GCF IL-1β levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.

Has the Covid-19 pandemic altered the frequency of periodontitis? An analysis conducted using Google Trends.

“…Wang et al investigated the causal relationship between periodontitis and SARS-CoV-2 infection based on MR (Mendelian Randomization) methods and concluded that there is a causal relationship between periodontitis and SARS-CoV-2 infection. [43] In their study, Meng et al found that periodontitis and GCF (Gingival crevicular uid) IL-1β (Interleukin-1β) levels, which are higher in periodontitis, are causally related to increased susceptibility to SARS-CoV-2 infection [21]. On the other hand, a study by Drozdzik et al showed that there was no causal connection between periodontitis and SARS-CoV-2 cases, but it was found that maintaining good periodontal health is positively correlated with the prognosis of the disease in SARS-CoV-2 patients [22].…”

“…It has also been reported that aspiration of saliva with a high viral load may carry the virus to the lower respiratory tract and increase the risk of developing more severe forms of the disease [42]. Numerous studies have investigated the potential presence of a relationship between periodontal diseases and SARS-CoV-2 infection [21,22,24]. Wang et al investigated the causal relationship between periodontitis and SARS-CoV-2 infection based on MR (Mendelian Randomization) methods and concluded that there is a causal relationship between periodontitis and SARS-CoV-2 infection.…”

“…The relationship between gingivitis, periodontitis, and SARS-CoV-2 has been investigated due to the presence of periodontal diseases among oral manifestations of SARS-CoV-2. [21][22][23] It has been determined that there is a relationship between periodontitis [24] and severe SARS-CoV-2 and that the probability of developing severe SARS-CoV-2 in patients diagnosed with periodontitis is 2.81 times higher [23]. In addition, another study found that SARS-CoV-2 patients with periodontitis had a higher rate of admission to intensive care units, mortality, and a greater need for ventilation [25,26].…”

Relationship between the Social Development Index and Self-Reported Periodontal Conditions

“…As already mentioned, several studies have considered the hypothesis of a possible association, even a causal role, between periodontitis and COVID-19 [112][113][114]. Their in-flammatory and infectious natures have been reported to be among the mechanisms linking both diseases [115,116].…”

A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis

“… 24 Given the urgency to investigate the potential causal link between periodontitis and coronary atherosclerosis. Scholars have employed MR analysis to study the relationship between periodontitis and multiple non-oral diseases, 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 including arthritis, hypertension, psoriasis, Parkinson's disease, inflammatory bowel disease (IBD), etc. However, most studies have not provided strong supporting a significant causal relationship between the periodontitis and these diseases, suggesting that periodontitis may be a comorbid condition or that other shared disease mechanisms are yet to be explored.…”